TOP一般口演(Oral)
 
Oral
Neural mechanisms for anxiety and depression
一般口演
不安・気分障害の神経メカニズム
7月26日(金)8:30~8:45 第8会場(朱鷺メッセ 3F 303+304)
2O-08m1-1
Collateral projections from lateral orbitofrontal cortex to nucleus accumbens and basolateral amygdala.
Chien-Wen Lai(Lai Chien-Wen)1,Chun-hui Chang(Chang Chun-hui)1,2
1Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, TAIWAN
2Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu, TAIWAN

The lateral orbitofrontal cortex (lOFC) projects to the nucleus accumbens (NAcc) and the basolateral nucleus of the amygdala (BLA). Each projection regulates different behaviors, such as compulsive drug seeking and reward outcome encoding. However, it is still unknown of whether the lOFC modulates the downstream targets simultaneously. In this study, we used in vivo extracellular single unit recordings in anaesthetized rats to examine the connection between lOFC and NAcc or BLA, and also tested if there are collateral projections from lOFC to NAcc and BLA. The stimulation electrodes were placed in the NAcc and BLA in search of antidromic or orthodromic responsive neurons in the lOFC. A total of 19 neurons were recorded from 10 rats. Among our sampled units, eight neurons projected from lOFC to NAcc with a latency of 8.34 ± 0.97 ms (range 4.49 to 12.01 ms), while five neurons projected from NAcc to lOFC with a latency of 6.85 ± 2.22 ms (range 1.36 to 11.72 ms). We found one neuron projected from lOFC to BLA with a latency of 6.77 ms, while four neurons projected from BLA to lOFC with a latency of 19.51 ± 2.22 ms (range 11.82 to 26.17 ms). Of all the neurons recorded, we only found one lOFC neuron collaterally projected to both NAcc and BLA with latencies of 4.39 ms and 13.52 ms, respectively. Under our filter settings (bandpass 300-10K Hz), 17 of the sampled neurons had low firing rate (0.23 ± 0.12 Hz, range 0 to 1.8 Hz) with relative long spike duration (2.53 ± 0.19 ms, range 0.38 to 3.60 ms), suggesting the majority of these units were putative projections neurons. The rest two of the sampled neurons (from NAcc to lOFC) had high firing rate (4.75 and 8.53 Hz) with short spike duration (0.80 to 0.78 ms), presumably were interneurons. Because of the low sampling rate of projections from lOFC to BLA, we further tested the threshold (the stimulation current to evoke spike response probability of 2 - 12%) of lOFC neurons projecting to NAcc or BLA. In our preliminary data, we found two neurons in NAcc responsive to lOFC stimulations from five rats, with a threshold at 0.35 and 0.40 mA. So far we did not find any responsive units in BLA. Our on-going experiments also supported the idea that the lOFC to BLA projections were sparse. We will next combine tracer study to examine if there is topographic segregation of NAcc and BLA projections from lOFC.
7月26日(金)8:45~9:00 第8会場(朱鷺メッセ 3F 303+304)
2O-08m1-2
Intense Threat Switches Dorsal Raphe Serotonin Neurons to a Paradoxical Operational Mode
Changwoo Seo(Seo Changwoo)1,2,Akash Guru(Guru Akash)1,2,Michelle Jin(Jin Michelle)3,Brendon Ito(Ito Brendon)1,Brianna J Sleezer(Sleezer Brianna J)1,Yi-Yun Ho(Ho Yi-Yun)1,2,Elias Wang(Wang Elias)4,Christiana Boada(Boada Christiana)5,Nicholas A Krupa(Krupa Nicholas A)1,Durgaprasad S Kullakanda(Kullakanda Durgaprasad S)1,Cynthia Shen(Shen Cynthia)1,Melissa R Warden(Warden Melissa R)1,2
1Department of Neurobiology and Behavior, Cornell University, Ithaca, USA
2Cornell Neurotech, Cornell University, Ithaca, USA.
3Neurobiology of Relapse Section, National Institute on Drug Abuse (NIDA), Baltimore, USA
4Department of Electrical Engineering, Stanford University, Stanford, USA
5School of Medicine, New York University, New York, USA.

Survival depends on the selection of behaviors adaptive for the current environment. For example, a mouse should run from a rapidly looming hawk but should freeze if the hawk is coasting across the sky. The decision to move or to refrain from movement depends on the structure of the environment and the internal state of the animal. Neuromodulatory systems receive input from brain regions that represent environmental structure and internal state and are essential for the coordinated regulation of the neural circuits that control movement. Although serotonin has been implicated in adaptive behavior, environmental regulation of its functional role remains poorly understood. Here, we have probed the neural dynamics and functional roles of two distinct dorsal raphe nucleus cell types (serotonin & GABA) in movement regulation. We found that stimulation of dorsal raphe serotonin neurons suppressed movement in low- and moderate-threat environments but induced escape behavior in high-threat environments, and that movement-related dorsal raphe serotonin neural dynamics inverted in high-threat environments. Stimulation of dorsal raphe GABA neurons promoted movement in negative but not positive environments, and movement-related GABA neural dynamics inverted between positive and negative environments. Thus, dorsal raphe circuits switch between distinct operational modes to promote environment-specific adaptive behaviors.
7月26日(金)9:00~9:15 第8会場(朱鷺メッセ 3F 303+304)
2O-08m1-3
Functional role of central amygdala input to the central sublenticular extended amygdala
Yajie Sun(Sun Yajie),Lei Qian(Qian Lei),Li Xu(Xu Li),Sarah Hunt(Hunt Sarah)
Queensland Brain Institute, The University of Queensland, Brisbane, Australia

Anxiety is one of the most prevalent and debilitating mental disorders, but its underlying neural mechanisms remain largely unknown. Several lines of evidence suggest that the central nucleus of the amygdala (CeA), and the central sublenticular extended amygdala (SLEAc), and the connections between them are essential components of the circuits that underpin anxiety behaviours. Using a combination of tract tracing, electrophysiology, and behavioural approaches, we have dissected the synaptic connections between the CeA and SLEAc, and their functional role in mice. Retrograde tracing experiments revealed that the most substantial projections from the CeA to SLEAc originate from the lateral division of the CeA (CeL), with the majority of the retrogradely labeled cells in the CeL expressing somatostatin (SOM). Using channelrhodopsin-2-assisted circuit mapping and whole cell patch-clamp recordings, we show that CeL SOM-expressing (SOM+) neurons innervate the SLEAc, with a preference for GABAergic neurons. Moreover, we find that the direct CeL input to SLEAc neurons is GABAergic, and strong enough to halt the firing of its downstream neuronal targets. Behavioural experiments using pharmacogenetic and optogenetic manipulations show that selective activation of either CeL SOM+ neurons or CeL-SLEAc circuits was anxiogenic, as assessed in open field test and elevated plus maze. These results define an inhibitory circuit between CeL and SLEAc, and show that SOM+ neurons in the CeL mediate anxiety by inhibiting GABAergic neurons in the SLEAc.
7月26日(金)9:15~9:30 第8会場(朱鷺メッセ 3F 303+304)
2O-08m1-4
ラード摂取が高脂肪食誘導性肥満ラットにおける不安様行動を引き起こす
Shingo Nakajima(中島 進吾)1,2,Mari Gotoh(後藤 真里)3,Keiko Fukasawa(深澤 桂子)2,Kimiko Murofushi(室伏 きみ子)2,Hiroshi Kunugi(功刀 浩)1
1国立精神・神経セ神経研疾病3
2お茶の水女子大学 お茶大アカプロ
3お茶の水女子大学 ヒューマンライフ

Background: Obesity is well known as a risk factor for neurodegenerative- and psychiatric- diseases including Alzheimer's disease, schizophrenia, and depression. Commercial high fat diet containing lard is well used to induce obesity in animal experiment, which also induces abnormal behavior such as anxiety-like and depression-like behaviors. However, it is still unclear the contribution of dietary fat source to the abnormal behaviors.
Methods: In the present study, Male Sprague-Dawley rats (8 weeks-old) were treated with different type of high fat (lard and olive oil)/high sucrose diet for more than 8 weeks. Anxiety-like behavior (Open-field test and social interaction test) and cognitive function (Y-maze test) were performed. Serum lipid species were determined using liquid chromatography equipped with tandem mass spectrometry. Prefrontal mRNA expression related to neurotransmitter and nutrient transporter were determined with real-time PCR.
Results: Both high fat/high sucrose diets increased body weight and adipose tissue. Only high lard/high sucrose (HL/HS) diet induced anxiety-like behavior in open field test and social interaction test. There was no correlation between body weight and anxiety-like behavior. Several lipid species were altered by HL/HS diet, and they were correlated to anxiety-like behavior. Further, HL/HS diet induced increase of glutamate transporter and decrease of glutamate receptor mRNA expressions in prefrontal cortex.
Conclusions: Daily intake of lard but not olive oil causes anxiety-like behavior in high fat diet-induced obesity in related to altered peripheral lipid composition.